tbuckley/cabot-search huggingface dataset:
Implementation of Patient-Reported Outcome Measures for Gender-Affirming Care Worldwide
Authors: Rakhshan Kamran, Liam Jackman, Cynthia Chan, Yujin Suk, Chloe Jacklin, Eve Deck, Nina Wietek, Melissa Stepney, Conrad Harrison, Abhilash Jain, Jeremy Rodrigues
Journal: JAMA Network Open (2023)

Importance Gender-affirming care is a key clinical area that can benefit from implementation of patient-reported outcome measures (PROMs). Identifying barriers to and enablers of PROM implementation is needed to develop an evidence-based implementation strategy. Objective To identify (1) PROMs previously implemented for gender-affirming care and constructs measured, (2) how patients completed PROMs and how results were reported and used, and (3) barriers to and enablers of PROM implementation. Evidence Review In this systematic review, PubMed, Embase, MEDLINE, PsycINFO, CINAHL, and Web of Science were searched from inception to October 25, 2021, and updated on December 16, 2022. Gray literature was searched through gray literature database, online search engine, and targeted website searching. Inclusion criteria were (1) original articles of (2) a formally developed PROM or ad hoc instrument administered for gender-affirming care to (3) patients accessing gender-affirming care. The Critical Appraisal Skills Programme tool was used to evaluate quality of included studies. This review was registered on PROSPERO (CRD42021233080). Findings In total, 286 studies were included, representing 85 395 transgender and nonbinary patients from more than 30 countries. A total of 205 different PROMs were used in gender-affirming care. No studies described using an implementation science theory, model, or framework to support PROM deployment. Key barriers to PROM implementation included issues with evidence strength and quality of the PROM, engaging participants, and PROM complexity. Key enablers of PROM implementation included using PROMs validated for gender-affirming care, implementing PROMs able to be deployed online or in person, implementing PROMs that are shorter and reduce patient burden, engaging key stakeholders and participants as part of developing an implementation plan, and organizational climate. Conclusions and Relevance In this systematic review of barriers to and enablers of PROM implementation in gender-affirming care, PROM implementation was inconsistent and did not follow evidence-based approaches in implementation science. There was also a lack of patient input in creating implementation strategies, suggesting a need for patient-centered approaches to PROM implementation. Frameworks created from these results can be used to develop evidence-based PROM implementation initiatives for gender-affirming care and have potential generalizability for other clinical areas interested in implementing PROMs.
Response by Butt et al to Letter Regarding Article, “Efficacy and Safety of Dapagliflozin According to Frailty in Patients With Heart Failure: A Prespecified Analysis of the DELIVER Trial”
Authors: Jawad H. Butt, Scott D. Solomon, John J.V. McMurray
Journal: Circulation (2023)

In Response:Drs Wong and Demers are of course correct that there is an association between frailty and age, but it is also well recognized that frailty can develop at any age.The frailty-associated gradient in age in any specific population likely reflects many different factors, including the disease in question, sex distribution, and the extent of comorbidity.Among patients with heart failure, all of these vary by ejection fraction phenotype.Many of these factors also vary by geographic region, and clinical trials may include patients from up to 50 countries.How frailty is assessed may also be relevant.Although it is interesting that the age gradient appeared greater in patients with reduced ejection fraction compared with preserved ejection fraction, in the trial publication mentioned by the authors 1 (and in a second article 1 ), this was not the case in another heart failure with reduced ejection fraction trial. 2 In 2 recent studies of "real-world" as opposed to trial patients, the age gradient related to frailty was small and similar to that observed in our analysis of the DELIVER trial. 3,4We do not agree that trials include few elderly patients.The proportion of patients ≥80 years of age in PARAGON-HF was 22.4%, and in DELIVER, it was 21.4%.The median age among patients from North America in each of these trials was 75 years, not so different from similar patients in the Get With the Guidelines-Heart Failure Registry (median age, 76 years). 5We see no reason not to apply the findings of trials to older patients because the benefits of treatment are generally consistent across the range of age in both heart failure with reduced ejection fraction and heart failure with midrange ejection fraction/heart failure with preserved ejection fraction.Indeed, what the studies of frailty and older age emphasize is the large absolute benefits of treatment in these vulnerable patients who are often needlessly denied therapy.
Measuring Moral Distress: Improving the Tools by Educating Clinicians
Authors: Lauren Boxell, Elizabeth Lanphier
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Moral Distress: What Are We Measuring? Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Targeting Mutated p53: Naivete and Enthusiasm to Attempt the Impossible
Authors: Wafik S. El-Deiry
Journal: Cancer Research (2023)

Abstract Tumor suppressor TP53 is an important gene in human cancer because it is mutated in the majority of tumors, leading to loss-of-function or gain-of-function phenotypes. Mutated TP53 acts like an oncogene, driving cancer progression and causing poor patient outcomes. The role of mutated p53 in cancer has been known for over three decades, yet there is no FDA-approved drug to address the problem. This brief historical perspective highlights some of the insightful advances as well as challenges in therapeutic targeting of p53, especially the mutated forms. The article focuses on a functional p53 pathway restoration approach to drug discovery that years ago was not mainstream, encouraged by anyone, taught in textbooks, or embraced by medicinal chemists. With some knowledge, a clinician scientist's interest, and motivation, the author pursued a unique line of investigation leading to insights for functional bypass of TP53 mutations in human cancer. Like mutated Ras proteins, mutant p53 is fundamentally important as a therapeutic target in cancer and probably deserves a "p53 initiative" like the NCI's "Ras initiative.” There is a link between naivete and enthusiasm for pursuing difficult problems, but important solutions are discovered through hard work and persistence. Hopefully, some benefit comes to patients with cancer from such drug discovery and development efforts.
Medicalized Oppression: Labels of “Violence Risk” in the Electronic Medical Record
Authors: Zamina Mithani, J. Wesley Boyd
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Materialized Oppression in Medical Tools and Technologies Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Self-Reported Primary Cooking Fuels Use and Risk of Chronic Digestive Diseases: A Prospective Cohort Study of 0.5 Million Chinese Adults
Authors: Qiaorui Wen, Tanxin Liu, Yuelin Yu, Yunjing Zhang, Yingzi Yang, Rongshou Zheng, Liming Li, Ru Chen, Shengfeng Wang
Journal: Environmental Health Perspectives (2023)

Household air pollution (HAP) from inefficient combustion of solid fuels is a major health concern worldwide. However, prospective evidence on the health impacts of solid cooking fuels and risks of chronic digestive diseases remains scarce.
The future of hepatology
Authors: Scott L. Friedman, Arun J. Sanyal
Journal: Hepatology (2023)

The field of hepatology has made impressive progress over its ~75 years of existence. Advances in understanding liver function and its dysregulation in disease, genetic determinants of disease, antiviral therapy, and transplantation have transformed the lives of patients. However, there are still significant challenges that require ongoing creativity and discipline, particularly with the emergence of fatty liver diseases, as well as managing autoimmune disease, cancer, and liver disease in children. Diagnostic advances are urgently needed to accelerate risk stratification and efficient testing of new agents with greater precision in enriched populations. Integrated, holistic care models should be extended beyond liver cancer to diseases like NAFLD with systemic manifestations or extrahepatic comorbidities such as cardiovascular disease, diabetes, addiction, and depressive disorders. To meet the growing burden of asymptomatic liver disease, the workforce will need to be expanded by incorporating more advanced practice providers and educating other specialists. The training of future hepatologists will benefit from incorporating emerging skills in data management, artificial intelligence, and precision medicine. Continued investment in basic and translational science is crucial for further progress. The challenges ahead are significant, but with collective effort, the field of hepatology will continue to make progress and overcome obstacles.
Defining the questions to be asked in severe asthma trials: data from the COMSA working group
Authors: Thomas Eiwegger, Sarah A. Bendien
Journal: European Respiratory Journal (2023)

<b>The COMSA consensus document is a big step forward to serve the demand for harmonised patient-centred COM sets for severe asthma treatment by including all relevant stakeholders</b>http://bit.ly/3UR4rge
Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results
Authors: Kelly C. Goldsmith, Julie R. Park, Kimberly Kayser, Jemily Malvar, Yueh-Yun Chi, Susan G. Groshen, Judith G. Villablanca, Kateryna Krytska, Lillian M. Lai, Patricia T. Acharya, Fariba Goodarzian, Bruce Pawel, Hiroyuki Shimada, Susan Ghazarian, Lisa States, Lynley Marshall, Louis Chesler, Meaghan Granger, Ami V. Desai, Rajen Mody, Daniel A. Morgenstern, Suzanne Shusterman, Margaret E. Macy, Navin Pinto, Gudrun Schleiermacher, Kieuhoa Vo, Holger C. Thurm, Joseph Chen, Marlon Liyanage, Gerson Peltz, Katherine K. Matthay, Esther R. Berko, John M. Maris, Araz Marachelian, Yael P. Mossé
Journal: Nature Medicine (2023)

Abstract Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib. We conducted a first-in-child study evaluating lorlatinib with and without chemotherapy in children and adults with relapsed or refractory ALK-driven neuroblastoma. The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12 months to &lt;18 years); lorlatinib as a single agent in adults (≥18 years); and lorlatinib in combination with topotecan/cyclophosphamide in children (&lt;18 years). Primary endpoints were safety, pharmacokinetics and recommended phase 2 dose (RP2D). Secondary endpoints were response rate and 123 I-metaiodobenzylguanidine (MIBG) response. Lorlatinib was evaluated at 45–115 mg/m 2 /dose in children and 100–150 mg in adults. Common adverse events (AEs) were hypertriglyceridemia (90%), hypercholesterolemia (79%) and weight gain (87%). Neurobehavioral AEs occurred mainly in adults and resolved with dose hold/reduction. The RP2D of lorlatinib with and without chemotherapy in children was 115 mg/m 2 . The single-agent adult RP2D was 150 mg. The single-agent response rate (complete/partial/minor) for &lt;18 years was 30%; for ≥18 years, 67%; and for chemotherapy combination in &lt;18 years, 63%; and 13 of 27 (48%) responders achieved MIBG complete responses, supporting lorlatinib’s rapid translation into active phase 3 trials for patients with newly diagnosed high-risk, ALK-driven neuroblastoma. ClinicalTrials.gov registration: NCT03107988 .
Nylon ring with titanium clip assists endoscopic cyanoacrylate injection for the treatment of GOV1-type gastric varices
Authors: Haijun Mou, Qi Liu, Yi Fan, Guoqing Shi, Huichao Wu, Biguang Tuo, Rui Xie
Journal: Endoscopy (2023)

There is an estimated approximately 20 % chance of having gastric varices in patients with portal hypertension [1]. Gastric varices bleed less frequently than esophageal varices but are much more severe when they do occur. Therefore, effective treatment of such bleeding or prevention of rebleeding is vital. According to the Baveno VI Consensus Symposium, endoscopic injection of cyanoacrylate is the recommended treatment for hemostasis and prevention of rebleeding from gastric varices [2] (de Franchis and Baveno 2015). However, a number of serious adverse events has been reported including ectopic embolism, especially in bleeding patients with gastric varices and gastrorenal shunts (GOV2 or IGV1 varices) [3] [4]. As an alternative to endoscopic therapy guided by endoscopic ultrasound (EUS) and balloon-occluded retrograde transvenous obliteration, we hope to provide a new simple and effective method for the treatment of GOV1 gastric varices. By using nylon rings and clips we attempted to completely block blood flow to the gastric varices before injecting cyanoacrylate into the gastric varices. This method can effectively reduce the risk of ectopic embolism in GOV1 gastric varices and reduce the dosage of cyanoacrylate.
Another Death
Authors: Nicholas John Batley
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Higher Genetic Risk Loads Confer More Diverse Manifestations and Higher Risk of Lupus Nephritis in Systemic Lupus Erythematosus
Authors: Young‐Chang Kwon, Eunji Ha, Hyuk‐Hee Kwon, Dae Jin Park, Jung‐Min Shin, Young Bin Joo, Won Tae Chung, Dae‐Hyun Yoo, Hye‐Soon Lee, Kwangwoo Kim, Sang‐Cheol Bae, So‐Young Bang
Journal: Arthritis & Rheumatology (2023)

Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients.We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome-wide single-nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well-validated non-HLA SNPs and HLA haplotypes of SLE-risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration.Childhood-onset SLE (<16 years) conferred the highest genetic risk compared with adult-onset (16-50 years) or late-onset (>50 years) SLE (P = 6.8 × 10-6 ). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10-6 ). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10-8 ) and anti-Sm antibody production (HR 1.85, P = 2.8 × 10-5 ). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10-5 ) and class V (HR 2.79, P = 1.0 × 10-3 ), but especially lupus nephritis class V in anti-Sm-positive SLE (area under the curve 0.68, P = 1.8 × 10-4 ).Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti-Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.
Editor's Note: Activator Protein-1 Transcription Factors Are Associated with Progression and Recurrence of Prostate Cancer
Authors: Xuesong Ouyang, Walter J. Jessen, Hikmat Al-Ahmadie, Angel M. Serio, Yong Lin, Weichung-Joseph Shih, Victor E. Reuter, Peter T. Scardino, Michael M. Shen, Bruce J. Aronow, Andrew J. Vickers, William L. Gerald, Cory Abate-Shen
Journal: Cancer Research (2023)

The editors are publishing this note to alert readers to a concern about this article (1). In Fig. 4A, the same image was used to show α-Jun expression in benign tissue and α-Fos expression in benign tissue.
New perspectives on respiratory syncytial virus surveillance at the national level: lessons from the COVID-19 pandemic
Authors: Anne C. Teirlinck, Caroline K. Johannesen, Eeva K. Broberg, Pasi Penttinen, Harry Campbell, Harish Nair, Rachel M. Reeves, Håkon Bøås, Mia Brytting, Wei Cai, AnnaSara Carnahan, Jean-Sebastien Casalegno, Kostas Danis, Cillian De Gascun, Joanna Ellis, Hanne-Dorthe Emborg, Manuel Gijon, Raquel Guiomar, Siddhivinayak S. Hirve, Helena Jiřincová, Hanna Nohynek, Jesus Angel Oliva, Richard Osei-Yeboah, John Paget, Gatis Pakarna, Richard Pebody, Lance Presser, Marie Rapp, Janine Reiche, Ana Paula Rodrigues, Elina Seppälä, Maja Socan, Karol Szymanski, Ramona Trebbien, Jaromíra Večeřová, Sylvie van der Werf, Maria Zambon, Adam Meijer, Thea K. Fischer
Journal: European Respiratory Journal (2023)

<b>Learning from the COVID-19 pandemic and considering the effects of this pandemic, we provide recommendations that can guide towards sustainable RSV surveillance with the potential to be integrated into the broader perspective of respiratory surveillance.</b> https://bit.ly/40TsO0G
Antagonizing apolipoprotein J chaperone promotes proteasomal degradation of mTOR and relieves hepatic lipid deposition
Authors: Shuangdi Duan, Nong Qin, Jiayi Pi, Pei Sun, Yating Gao, Lamei Liu, Zenghui Li, Ya Li, Liyang Shi, Qiang Gao, Ye Qiu, Songqing Tang, Chun-Hsiang Wang, Tzu-Ying Chen, Sin-Tian Wang, Kung-Chia Young, Hung-Yu Sun
Journal: Hepatology (2023)

Background and Aims: Overnutrition-induced activation of mammalian target of rapamycin (mTOR) dysregulates intracellular lipid metabolism and contributes to hepatic lipid deposition. Apolipoprotein J (ApoJ) is a molecular chaperone and participates in pathogen-induced and nutrient-induced lipid accumulation. This study investigates the mechanism of ApoJ-regulated ubiquitin-proteasomal degradation of mTOR, and a proof-of-concept ApoJ antagonist peptide is proposed to relieve hepatic steatosis. Approach and Results: By using omics approaches, upregulation of ApoJ was found in high-fat medium-fed hepatocytes and livers of patients with NAFLD. Hepatic ApoJ level associated with the levels of mTOR and protein markers of autophagy and correlated positively with lipid contents in the liver of mice. Functionally, nonsecreted intracellular ApoJ bound to mTOR kinase domain and prevented mTOR ubiquitination by interfering FBW7 ubiquitin ligase interaction through its R324 residue. In vitro and in vivo gain-of-function or loss-of-function analysis further demonstrated that targeting ApoJ promotes proteasomal degradation of mTOR, restores lipophagy and lysosomal activity, thus prevents hepatic lipid deposition. Moreover, an antagonist peptide with a dissociation constant (Kd) of 2.54 µM interacted with stress-induced ApoJ and improved hepatic pathology, serum lipid and glucose homeostasis, and insulin sensitivity in mice with NAFLD or type II diabetes mellitus. Conclusions: ApoJ antagonist peptide might be a potential therapeutic against lipid-associated metabolic disorders through restoring mTOR and FBW7 interaction and facilitating ubiquitin-proteasomal degradation of mTOR.
Correction: ARF Confers a Context-Dependent Response to Chemotherapy in Muscle-Invasive Bladder Cancer
Authors: Tomasz B. Owczarek, Takashi Kobayashi, Ricardo Ramirez, Lijie Rong, Anna M. Puzio-Kuter, Gopa Iyer, Min Yuen Teo, Francisco Sánchez-Vega, Jingqiang Wang, Nikolaus Schultz, Tian Zheng, David B. Solit, Hikmat A. Al-Ahmadie, Cory Abate-Shen
Journal: Cancer Research (2023)

In the original version of this article (1), there was an error in Fig. 3C. Specifically, the same Ki67/DAPI immunofluorescence image was used for both UMUC3-Control cells treated with vehicle and UMUC3-shITGB3BP cells treated with cisplatin. The correct images have been provided and the error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Translating neonatal microbiome science into commercial innovation: metabolism of human milk oligosaccharides as a basis for probiotic efficacy in breast-fed infants
Authors: David A. Mills, J. Bruce German, Carlito B. Lebrilla, Mark A. Underwood
Journal: Gut Microbes (2023)

For over a century, physicians have witnessed a common enrichment of bifidobacteria in the feces of breast-fed infants that was readily associated with infant health status. Recent advances in bacterial genomics, metagenomics, and glycomics have helped explain the nature of this unique enrichment and enabled the tailored use of probiotic supplementation to restore missing bifidobacterial functions in at-risk infants. This review documents a 20-year span of discoveries that set the stage for the current use of human milk oligosaccharide-consuming bifidobacteria to beneficially colonize, modulate, and protect the intestines of at-risk, human milk-fed, neonates. This review also presents a model for probiotic applications wherein bifidobacterial functions, in the form of colonization and HMO-related catabolic activity in situ, represent measurable metabolic outcomes by which probiotic efficacy can be scored toward improving infant health.